Multi-particulate Novel Drug Delivery Systems Based On Gelucire 39/01 and 50/13

1. E
Presented by:
Shashank Soni
Assistant Professor
School of Pharmaceutical Sciences
Sardar Bhagwan Singh PG Institute of Bio Medical Sciences
and Research, Dehradun
How to cite this article:
http://www.revistafarmacia.ro/201701/art-23-Soni_Verma_INDIA_142-152.pdf

2.  The purpose of the present investigation is to study the effect of incorporation of Gelucire
39/01 and 50/13 on encapsulation efficiency and release of water soluble and insoluble drugs
(Metronidazole , log P= 0.0 and Norfloxacin, log P= 1.5) from floating alginate beads.
Floating beads (with or without drug) were prepared by extruding dropwise with the help of a
hypodermic needle an emulsion of sodium alginate (SA) with Gelucire 39/01 and 50/13
containing CaCO3 into CaCl2 solution prepared in 10% v/v acetic acid. Beads formed
instantaneously were cured for 10 min in the gelation medium at 370
C. Prepared beads showed
excellent buoyancy in vitro, significantly (p<0.05) improved encapsulation efficiency and
sustained release of model drugs. In conclusion, these beads may form a potential stomach site
specific drug delivery system for the delivery of both water soluble and insoluble drugs with
absorption window in upper gastrointestinal tract.
 Key words: Alginate beads, floating drug delivery systems, Gelucire, Metronidazole,
Norfloxacin

3.  Floating Ca++
induced alginate beads have been developed in recent years
as a unique vehicle for stomach specific drug delivery. These beads can be
frequently produced by extruding a solution of SA containing a gas-
generating agent (CaCO3 or NaHCO3) into a divalent (Ca++
) crosslinking
solution in acetic acid (generally 10% v/v) .
 However, these beads often suffers from poor drug loading due to drug
loss during preparation by leaching through the pores in the beads and/or
fast drug release in acidic medium. A number of efforts have been made in
past to overcome these demerits.

4.  These include use of different gas-generating agents; incorporation of
vegetable oils and other additives into alginate beads. But these
modifications often lead to the systems which are difficult to reproduce or
scale up or not acceptable for human use due to presence of traces of
chemical crosslinker.
 In our quest to search techniques to overcome the demerits of alginate
beads, we did extensive experimentation in our laboratory and investigated
the feasibility of combining Gelucire 39/01 and 50/13 with SA to produce
floating emulsion gel beads by ionotropic gelation with Ca++
.

5.  Although SA promptly formed the emulsion with Gelucire 39/01, the
reason for incorporating Gelucire 50/13 was to promote further
emulsification of SA with Gelucire 39/01 and to prevent the excessive
retardation of drug release due highly lipophilic nature of Gelucire 39/01.
 The buoyancy to the beads was attributed to the use of CaCO3. The reason
for choosing the Gelucires as lipid phase was their excellent potential
against rancidity. The prepared Gelucire based emulsion gel beads are
expected to be superior to emulsion gel beads reported by various workers
in the respect that there would be no leakage of oil from the beads as
Gelucires are solid at room temperature.

6.  Further, in most of the studies vegetable oils were used, which are
susceptible to oxidation, whereas, Gelucires are least susceptible to
oxidation.
 In the present study, we prepared two sets of Gelucires based floating
emulsion gel bead formulations containing model drugs Metronidazole
(MTZ) and Norfloxacin (NFC) respectively.
 The prepared bead formulations are expected to retard the release of
embedded drugs in the acidic environment of stomach with improved
encapsulation efficiency.

7.  Selection and characterization of drug molecules (Metronidazole base
and Norfloxacin) by UV, FTIR, DSC analytical methods.
 Selection of polymers and other excipient for formulation of floating
emulsion gel beads like Gelucire, Sodium alginate used in
combination or may be used alone.
 Preformulation studies of polymers, excipient and drugs.
 Formulation of emulsion gel beads by emulsion gellation technique.

8. • Characterization of emulsion gel beads by following parameters.
 Study of drug-polymer interaction
 Conformation of emulsion gel beads
 Surface topography of gelled beads
 Swelling index of the beads
 Drug entrapment efficiency of the beads
 In vitro drug release of the beads
 Release Kinetics study of the beads

9.  Analysis of Drugs
 Fourier transforms infrared spectroscopy (FTIR)
 Ultraviolet absorption for estimation of λmax.
 Differential scanning calorimetry (DSC) study
 Quantitative Estimation of Drugs
 Determination of absorption maxima
 Preparation of 0.1 N HCl Buffer pH 1.2
 Media for Preparation of Standard Curve
 Preparation of Standard Curve

10.  Characterization of emulsion gel beads
 Drug excipient interaction studies
 Morphology and beads size determination
 In vitro buoyancy estimation
 In vitro release profile studies
 Determination of Drug entrapment efficiency
 Release kinetics of drug release by Zero order, First order, Higuchi role
model, Korsmeyer and peppas model

11.  Materials
Metronidazole (MTZ) and Norfloxacin (NFC) was gifted by Simpex
Laboratories Kotdwar, India. Sodium alginate was purchased from Sigma-
Aldrich (St. Louis, USA). Gelucire 39/01 (waxy solid, melting point 39 0
C,
HLB = 01) and 50/13 (melting point 500
C, HLB = 13) was a gift from
Gattefosse SAS (St Priest, Cedex, France). Water used in the formulations
was of HPLC grade (Merck) and all other chemicals used were of
analytical grade.

12.  Methods
Preparation of SA-Gelucire emulsion
The SA-Gelucire emulsion was prepared by mixing SA solution with a
mixture of molten Gelucires (39/01 and 50/13) with the help of a
mechanical stirrer at around 500 rpm for 5 min.
Preparation of floating emulsion gel beads
Floating emulsion gel beads were prepared by (Table 1) by extruding an
emulsion of SA with Gelucire 39/01 and 50/13 containing CaCO3 (with or
without drug) with the help of 25 ml hypodermic syringe, into CaCl2
solution (3%w/v in 10% v/v acetic acid) at room temperature (280
C). The
beads formed instantaneously, were cured for 10 minutes in gelation
medium at 37 0
C with mild agitation.

13.  Prepared beads were separated by filtration, washed thrice with deionized
water and dried in an oven at 35 0
C for 12 hours than kept in a desiccator
for another 12 hours before further experiments.
 Further, floating alginate beads without Gelucires were also prepared for
comparison purposes. These beads were prepared by extruding dropwise a
solution of SA in deionized water containing CaCO3 (with or without drug)
into CaCl2 solution (3 %w/v in 10% v/v acetic acid) at room temperature.

14. FORM.
CODE
MTZ
(mg)
NFC
(mg)
SA
(% w/v)
GELU.
39/01
(mg)
GELU.
50/13
(mg)
CaCO3
(% w/v)
Cacl2
(% w/v)
M 100 1.5 1 3
M1 100 1.5 50 16 1 3
M2 100 1.5 30 10 1 3
M3 100 1.5 25 5 1 3
M4 100 1.5 20 5 1 3
M5 100 1.5 30 5 1 3
N 100 1.5 1 3
N1 100 1.5 50 16 1 3
N2 100 1.5 30 10 1 3
N3 100 1.5 25 5 1 3
N4 100 1.5 20 5 1 3
N5 100 1.5 30 5 1 3

15.  The most important property of alginates is their ability to form gels by
reaction with divalent cations such as Ca++
. Monovalent cations and Mg++
do
not induce gelation of alginates.
 The gelation and crosslinking of SA are mainly achieved by the exchange
of Na+
from the guluronic acids with Ca++
, and stacking of these guluronic
groups to form the characteristic egg- box structure. The Ca++
bind to the α-
L-guluronic acid blocks in a highly cooperative manner and the size of the
cooperative unit is more than 20 monomers. Each alginate chain dimerizes
to form junctions with many other chains and as a result gel networks are
formed .

16.  The Ca++
reactivity to alginates is the result of Ca++
induced dimeric
association of G-block regions.
Figure 1. Egg box association of poly L- guluronate sequences of alginate and
conversion of random coils to ribbon structures when cross linked with ca2+
ions.

17.  When an emulsion of SA with Gelucires containing CaCO3 was extruded
into acidic CaCl2 solutions, porous gel beads were formed instantaneously
due to simultaneous gas-generation and ionotropic gelation in which
intermolecular cross-links were formed between the Ca++
and the negatively
charged COO-
groups of SA.
 The prepared beads were cured in the gelation medium for 10 min at 37 0
C.
It was observed that when the beads were prepared at room temperature
(280
C), they sank rapidly and there was no floating of dried beads.
Therefore, we have experimented the preparation of beads at different
temperatures and as result 370
C temperature was selected.

18.  The preparation and curing at this temperature facilitated the diffusion of
acidic gelation medium inside the bead structure in order to expedite the
reaction between gas-generating agent and acetic acid present in gelation
medium. The dried beads obtained from this procedure exhibited
prolonged floating when placed on 0.1 M HCl.

19. The absorption maxima for the drug (MTZ) is determined by UV
spectrophotometer and was found to be 278 nm when scanned between
200-400nm as shown in fig:
Fig2: Absorption maxima of Metronidazole base in 0.1M HCl (pH 1.2)

20. The absorption maxima for the drug (NFC) is determined by UV
spectrophotometer and was found to be 278 nm when scanned between
200-400nm as shown in fig:
Fig 3: Absorption maxima of Norfloxacin in 0.1M HCl at 278 nm (pH 1.2)

21. S.N0. CONC.
(mcg/ml)
ABS.
(nm)
1 0 0
2 2 0.101
3 4 0.186
4 6 0.277
5 8 0.351
6 10 0.422

22. S.N0. CONC.
(mcg/ml)
ABS.
(nm)
1 0 0
2 2 0.120
3 4 0.178
4 6 0.252
5 8 0.308
6 10 0.368

23. Parameters for MTZ. Drug Parameters for NFC. Drug
S.NO. PARAMETERS VALUES
1 Regression
coefficient
0.9962
2 Intercept on Y-
axis
0.012
3 Equation of
line
Y=0.0422x+0.
012
S.NO. PARAMETERS VALUES
1 Regression
coefficient
0.9816
2 Intercept on
Y-axis
0.0273
3 Equation of
line
Y=0.0354x+0.
0273

24. Figure 4. FTIR spectrums of Metronidazole and Norfloxacin

25.  The FTIR spectra of pure MTZ (Fig. 3) exhibited bands appearing at 2951,
2848 and 3098cm-1
due to C-H stretching. The bands at 1536 and 1366 are
due to N=O asymmetrical and symmetrical stretching. The bands at 1268
and 3220cm-1
are due to C-O and O-H stretching. The band due to
characteristic C-N stretching was seen at 1157cm-1
. Additionally
characteristic band of drug C=N stretching appeared at around 1480cm-1
.
 The FTIR spectra of pure NFC (Fig. 3) exhibit a band at 1033cm-1
due to
C-F stretching (mono fluorinated compound). The bands appearing at 1730
and 1617cm-1
due to C=O stretching of carboxylic and carbonyl group
respectively. The band at 1483 is due to –CH; deformation of –CH2. The
band at 1382cm-1
is due to the C-H bending, whereas bands at 3416, 2844
and 2553 cm-1
are due to O-H, C-H and N-H stretching vibrations
respectively.

26. Figure 5. FTIR spectrum of Sodium alginate

27.  FTIR spectrum of sodium alginate (Fig 4) is attributed to its saccharide
structure. The bands at 1620 and 1415 cm-1
are assigned to asymmetric and
symmetric stretching bands of carboxylate groups. The bands at 3435 and
2928 cm-1
are assigned to O-H stretching and C-H stretching in –CH2.

28. Figure 6. FTIR spectrum of Gelucire 39/01 and 50/13

29.  Gelucire are polyethylene glycol glycerides composed of mono-, di- and
triglycerides and mono- and diesters of polyethylene glycol (PEG).
Gelucire 39/01 is glycerol esters of saturated C12-C18 fatty acids,
whereas, Gelucire 50/13 is PEG-32 glyceryl palmitostearate. The FTIR
spectrum of Gelucire 39/01 showed characteristic bands at 1105, 1464, and
1742 cm-1
corresponding to C-O , C-H vibration of CH2 and C=O stretching
vibrations of esters respectively. The bands at 2922, 2853 cm-1
are due to
C-H str. (asymmetric and symmetric). Whereas, the FTIR spectrum of
Gelucire 50/13 showed characteristic bands at 1105, 1638 and 1738 cm-1
assigned to C-O stretching of esters, C=C and C=O stretching vibrations.
The bands at 2847, 2884, 2919 cm-1
are due to C-H stretching vibrations.

30. Figure 7. FTIR spectrum of Metronidazole and Norfloxacin formulations

31.  The FTIR spectrum of blank floating calcium alginate beads without
Gelucires was also recorded along with MTZ and NFC loaded
formulations to provide aid in interpretation of drug-excipient interactions.
The FTIR spectra of blank floating calcium alginate beads without
Gelucires exhibited characteristic bands at 1550 cm-1
indicating
involvement of COO-
group in coordination process with Ca++
; 1748 cm-1
indicates that some COO-
group of the SA transformed into carboxylic
group due to interaction with Ca++
and 3434 cm-1
indicating involvement of
hydroxyl group with Ca++
. The FTIR spectrum of NFC loaded formulation
showed characteristic bands at 1104, 1421, 1622, 1741, 2923, 2854 and
3438 cm-1
, whereas, MTZ loaded formulation exhibited characteristic bands
at 1268, 1462, 1744, 2924, 2854, 3099, 3224 and 3428 cm-1
. This suggests
that all the major bands of drugs were intact and there was no evidence of
interaction.

32. Figure 8. DSC thermograms of Metronidazole and Norfloxacin

33.  The DSC profile (Fig. 8) of NFC showed a sharp endothermic peak at
223.92 0
C and an exothermic peak at 287 0
C corresponding to the melting
point and degradation of NFC. The DSC profile (Fig. 8) of MTZ base
showed a sharp endothermic peak at 162.52 0
C corresponding to the
melting point of drugs.

34. Figure 9. DSC thermograms of sodium alginate, Gelucire 50/13 and 39/01

35.  The DSC thermogram of SA exhibited two endotherms at 146 and 210 0
C,
corresponding to the dehydration of water and very slow melting of SA.
The DSC thermogram of Gelucire 39/01 showed two endothermic peaks at
35 and 44 0
C, whereas , thermogram of Gelucire 50/13 showed (Fig. 9) a
broad endothermic peak at 46 0
C.

36.  The DSC thermogram of MTZ emulsion beads (Fig.9) bearing exhibited
three endothermic and one exothermic peak. The first endothermic peak
(very weak) at around 40 0
C could be attributed to the melting of Gelucires,
whereas, the second endothermic peak (broad) at 69 0
C could be attributed
to dehydration of water, whereas, the third endothermic peak at 160 0
C
could be attributed to the melting of MTZ. The exothermic peak at 246 0
C
could be attributed to the degradation of SA in the beads.
 On the other hand, in the DSC thermogram of NFC emulsion bead
formulations, the melting endotherm of NFC is missing indicating intimate
mixing of NFC in the Gelucires-SA emulsion. The data obtained from the
thermal studies exclude the possibility of interaction between drug,
Gelucires and SA.

37.  The scanning electron micrographs (SEM) of various MTZ and NFC
loaded floating emulsion beads are shown in Figure 8. The SEM results
revealed that NFC loaded floating emulsion beads were spherical in shape,
whereas, MTZ loaded floating emulsion beads were relatively irregular in
shape with rough outer surfaces (Fig 10).
 The transverse section of both MTZ and NFC loaded floating emulsion
beads showed a large hollow cavity along with numerous smaller internal
pores (Fig 10), attributed to the use of gas-generating agent.

38.  Upon contact with an acidic medium, CaCO3 effervesced, releasing CO2.
The released CO2 slowly diffused through the gel network due to high
viscosity of emulsion, with internal crosslinking of SA with released Ca++
producing a cross-linked three-dimensional gel network that restricted
further diffusion of CO2 and resulted in entrapment of released CO2 inside
the bead structure, thus, producing hollow cavity.

39. Figure 10. SEM images of MTZ and NFC loaded formulations at various magnifications. (a)
Shape of NFC loaded emulsion beads (b) surface morphology of NFC loaded floating emulsion
beads (c) transverse section of NFC loaded emulsion beads (d) Shape of MTZ loaded floating
emulsion beads (e) surface morphology of MTZ loaded floating emulsion beads (f) transverse
section of MTZ loaded floating emulsion beads

40.  The buoyancy of the beads was not dependent upon the lipid phase, i.e.,
Gelucires, as the emulsion beads prepared without the use of gas
generating agent sank rapidly. On the other hand, emulsion beads prepared
with gas-generating agent remained buoyant on 0.1 M HCl for sufficiently
long duration of time. Both floating emulsion beads remained buoyant for
upto 18 hours on 0.1 M HCl with no floating lag time. Whereas floating
beads (M and N) prepared without Gelucires floated for about 14 hours on
0.1 M HCl. Upon contact with an acidic medium, the CaCO3 effervesced,
releasing CO2. The released CO2 was entrapped in the gel network
producing buoyant formulation and thus, prolonged floating of emulsion
beads.

41.  It was also observed that in case of MTZ loaded emulsion beads, at higher
concentration of Gelucire 50/13 in the emulsion (M1), % buoyancy of the
beads was decreased. This could attributed to the formation of
comparatively more viscous emulsion (M1 compared M2, M3, M4 and
M5) due to the more efficient emulsification. When this emulsion was
extruded dropwise into the acidic gelation medium, the formation of dense
interior of the beads restricted the complete reaction between gas-
generating and acetic acid present in the gelation medium.

42.  However, this effect was not observed with NFC loaded emulsion beads.
The possible explanation for this observed difference could be the uniform
distribution of insoluble NFC in the emulsion. At higher Gelucire 50/13
concentration, although a viscous emulsion was formed but it seems that
NFC remained insoluble and uniformly distributed in the emulsion. This
might have resulted in the easy ingress of acetic acid present in the
gelation medium in to the emulsion due to somewhat porous interior
conferred by insoluble NFC, leading to complete reaction with gas-
generating agent and thus improved buoyancy (N1 compared to M1) of the
resultant beads.

43.  The effects of various formulation parameters on the entrapment efficiency
of the prepared floating emulsion beads are depicted in Table 2.

44. BAR GRAPH REPRESENTING % E.E
OF MTZ. FORMULATIONS
BAR GRAPH REPRESENTING % E.E
OF NFC. FORMULATIONS

45.  The entrapment efficiency of prepared MTZ loaded floating emulsion
beads varied from 63 to 82 % (Fig. 10), whereas, the entrapment efficiency
of NFC loaded floating emulsion beads ranged from 76-84 % (Fig. 10).
The floating beads prepared without Gelucires showed entrapment
efficiency, 41.32 % (M) and 51.64 % (N) respectively. There was
significant difference (p< 0.05) in entrapment efficiency between floating
emulsion beads and floating beads prepared without Gelucires. This
increase in entrapment efficiency could be attributed to the use of
lipophilic Gelucire 39/01 in the preparation of floating emulsion beads.

46.  This observation is consistent with the findings of (Murata et al., 2001)
who reported increased MTZ entrapment efficiency of emulsion gel beads
compared to calcium alginate beads. Further, these authors reported
maximum MTZ entrapment (76 %) at 30 % oil concentration, whereas, in
our case maximum MTZ entrapment efficiency (82 %) was found at very
low Gelucires concentration (M4).
 It was also observed that, in case of MTZ loaded floating emulsion beads,
as the concentration of Gelucire 50/13 was reduced in the emulsion, drug
entrapment efficiency of the emulsion beads increased significantly (M1
compared to M2, M3, M4 and M5, p< 0.05).

47.  This could be attributed to the high HLB of Gelucire 50/13, which when
used in high concentration, as in case of formulation M1, not only reduced
the hydrophobicity of emulsion but also affected the aqueous solubility of
MTZ, which in turn resulted in comparatively easy diffusion of water soluble
drug through the beads during processing in warm (37 0
C) acidic gelation
medium.
 However, this effect was not observed with NFC loaded emulsion beads. In
this case, it seems that, although the hydrophobicity of the emulsion was
decreased but high concentration of Gelucire 50/13 could not affect the
aqueous solubility of NFC, which retarded the diffusion of drug through the
beads during processing. However, NFC is reported to be an amphoteric
molecule, whose solubility increases as the pH of the medium is reduced to
below 4, but this effect was not observed with NFC loaded emulsion beads.

48.  The in vitro drug release profiles of MTZ and NFC from floating emulsion
bead formulations carried out in 0.01 M HCl (pH 1.2) are shown in Figure
11and 12.
Figure 11. Release profile of Metronidazole base in 0.01M HCl (pH 1.2)

49. Figure 12. Release profile of Norfloxacin in 0.01M HCl (pH 1.2)

50. DRUG RELEASE STUDIES OF METRONIDAZOLE BASE
 The drug release from all the MTZ loaded formulations was significantly
extended (upto 12-16 hours) compared to conventional floating calcium
alginate (upto 3 hours) beads (p< 0.05, M compared to M1, M2, M3, M4
and M5). There was ‘burst’ MTZ release from conventional floating
calcium alginate beads with about 60% of drug was released within first
hour and entire MTZ was emptied at the end of second hour. However,
incorporation of Gelucire 39/01 resulted in decreased release rates of
MTZ. This observation is consistent with the findings of Murata et al, who
reported decreased MTZ release rates from emulsion gel beads. From
formulation M1, around 13, 51, 75 and 99 % MTZ was released at the end
of 1st
, 8th
, 12th
and 15th
hour.

51.  Formulations M2, M3, M4 and M5 were prepared to study the effect of
different combinations of Gelucire 39/01 and Gelucire 50/13 on drug
release. From formulation M2, about 18, 50, 75 and 99 % MTZ was
released at the end of 1st
, 6th
, 11th
and 15th
hour. The MTZ release from
formulation (M2) was significantly fast (p<0.05) from formulation M1.
This could be attributed to the reduced hydrophobicity of the formulation
together with decreased solubilizing effect of Gelucire 50/13 on MTZ
solubility in aqueous medium. In case of formulation M3, concentrations
of both Gelucire 39/01 and 50/13 was further reduced which has resulted
in MTZ release rate which has almost similar to M2 and there was no
significant difference (p>0.05) in release rate.

52.  In case of formulation M4, the Gelucire 50/13 concentration was kept
constant, whereas, concentration of Gelucire 39/01 was further reduced.
This has resulted in MTZ release rate which was significantly fast from
M2 (p<0.05, M2 compared to M4), with approximately 22, 48, 75 and 99
% MTZ was released at the end of 1, 4, 8 and 12 hour. In case of
formulation M5, Gelucire 39/01 concentration was increased while
Gelucire 50/13 concentration kept constant. The MTZ release rate was
significantly retarded with approximately 6, 51, 72 and 99 % MTZ was
released at the end of 1, 8, 11 and 16 hour, which was significantly
different (p<0.05) from formulations M2, M3 and M4.

53. DRUG RELEASE STUDIES OF NORFLOXACIN :-
 The drug release from all NFC loaded formulations was also significantly
extended (upto 12-16 hours) compared to conventional NFC loaded
floating calcium alginate formulation (upto 3 hours). Here also, the NFC
release from calcium alginate beads was very rapid with about 55 % NFC
was released at the end of 1st
hour and almost entire drug was released at
the end of 3rd
hour. From formulation N1, around 24, 50, 74 and 99 % NFC
was released at the end of 1st
, 6th
, 10th
and 15th
hour. As the fraction of
Gelucire 39/01 was reduced in the emulsion bead formulation (N2), NFC
release was significantly increased (p< 0.05), with 25, 49, 77 and 99 %
NFC was released at the end of 1st
, 4th
, 8th
and 12th
.

54.  On the other hand reducing the amount of Gelucire 50/13, resulted in
significant retardation of NFC release (N3 and N5 compared to N2, p<
0.05). From formulation N4, around 30, 48, 79 and 99 % NFC was
released at the end of 1st
, 3rd
7th
and 10th
hour which was significantly
different from formulation N3 and N5 (p<0.05), which released
approximately 20, ≈49, ≈73, 99 % NFC at the end of 1st
, 7th
, 10th
and 16th
hour.

55.  The in vitro release pattern of various formulations was analyzed by fitting
the dissolution data into various kinetic models (Table 3). In case of MTZ
loaded emulsion beads, It was observed the for the formulations M1, M2,
M3 and M4, the r2
values were higher when fitted to zero order kinetics,
which describes that the drug release rate from the formulations is
independent of the concentration of the drug . For formulation M5, the r2
values was higher when fitted to Higuchi model, which describes the
release from system, where the solid drug is dispersed in an insoluble
matrix, and the rate of drug release is related to the rate of drug diffusion.

56.  The n values from drug release experiment ranged from 0.58-0.77,
indicated anomalous non-Fickian transport, which suggest that mechanism
and kinetics of drug release were dependent on the solubility of MTZ in
dissolution medium, with MTZ being predominantly released by diffusion
and anomalous behaviour resulting from the relaxation of macromolecular
polymeric chains in emulsion gel beads.

57.  In case of NFC loaded emulsion beads, formulation N1, N3 and N5
followed zero order kinetics as evidenced by r2
values, which were higher
when fitted to zero order kinetics. Whereas, formulations N2 and N4,
followed Higuchi kinetics, as evidenced by r2
values. The n values from
drug release experiment ranged from 0.44-0.55, with formulations N1 and
N4 followed Quasi-Fickian diffusion and formulations N2, N3 and N5
followed anomalous non-Fickian diffusion.

58. FORM.
CODE
ZERO
ORDER
(R2
VALUE)
FIRST
ORDER
(R2
VALUE)
HIGUCHI
(R2
VALUE)
KORSMEYE
R- PEPPA’S
(R2
VALUE)
n
VALUE
M1 0.9954 0.7302 0.9106 0.9227 0.76
M2 0.9891 0.6188 0.9627 0.9269 0.60
M3 0.9791 0.5787 0.9781 0.9777 0.60
M4 0.9957 0.7915 0.9107 0.9897 0.77
M5 0.9742 0.5548 0.9839 0.9974 0.58
TABLE 3 RELEASE KINETICS OF MTZ FROM
FABRICATED GEL BEADS

59. FORM.
CODE
ZERO
ORDER
(R2
VALUE)
FIRST
ORDER
(R2
VALUE)
HIGUCHI
(R2
VALUE)
KORSMEY
ER-
PEPPA’S
(R2
VALUE)
n VALUE
N1 0.9739 0.5321 0.9709 0.9829 0.44
N2 0.9641 0.5289 0.9894 0.9906 0.52
N3 0.9846 0.5735 0.9741 0.9914 0.55
N4 0.9525 0.5195 0.9926 0.9976 0.48
N5 0.9896 0.5927 0.9643 0.9802 0.55

60.  In this study, we have prepared Gelucire based floating emulsion gel beads
formulations and examined their drug encapsulation efficiency and release
characteristics by loading water soluble (MTZ) and water insoluble drugs
(NFC) separately.
 Prepared beads showed high drug encapsulation efficiency; excellent
buoyancy and released the model drugs MTZ and NFC gradually in 0.1 M
HCl. These properties are not only applicable to the sustained release of
the drugs with absorption window in the upper GIT but also to the stomach
specific drug delivery.

61.  These beads appears to be superior to previously reported emulsion gel
bead systems as the lipid phase (Gelucire 30/01 and 50/13) used is least
susceptible to rancidity and also there will be no leaking of lipid phase as it
is solid even at temperature upto 300
C.
 We propose that the prepared alginate based emulsion gel beads thought to
be able to sustain the release of both hydrophilic and hydrophobic drugs
over 12 h, while remaining afloat in gastric fluid.

62.  I am very thankful to my guide Prof. Anurag Verma and all the faculty
members of IFTM, Moradabad, I would also like to extreme my special
votes of thanks to CSIF; Jamia Hamdard University, Department of
Chemistry and Department of Textile technology; IIT New Delhi (India)
for the characterization of my samples during dissertation work. I am also
thankful to Dr. Alok Mishra, COO, Simpex laboratories, India and my gift
samples supplier Gattefosse, France for supplying the samples in time.

63.  This presentation is for knowledge and information only.
 This research work freely available and cite this article as
Shashank Soni, Navneet Verma, Anurag Verma*, Jayanta K Pandit.
Gelucire Based Floating Emulsion Gel Beads: A Potential Carrier for
Sustained Stomach Specific Drug Delivery. FARMACIA. 65 (1): 142-152
(2017). ISSN: 0014-8237.
 http://www.revistafarmacia.ro/201701/art-23-Soni_Verma_INDIA_142-152.pdf